The incorporation of materials science, cellular biology and engineering together with other fields such as chemistry and biochemistry has contributed to the expansion of modern medicine. The integration of the physical and life sciences helps address a number of the key issues in fields such as biomaterials and tissue engineering with the goal of bringing functional and practical devices or implants to the patient. Engineered tissue scaffolds and implantable materials must maintain physical and mechanical properties necessary to withstand the dynamic conditions present within the body and be biocompatible.
A number of materials and a variety of scaffold designs have been investigated for use as tissue engineering matrices for bone regeneration applications. Ideally, the scaffold is a porous, three-dimensional structure capable of maintaining structural integrity and allowing for cellular influx, growth, extracellular matrix (ECM) deposition, and metabolic exchange. The properties of the scaffold should be tailorable to control degradation rate, degree of porosity, and mechanical strength in order to closely match that of the host tissue. The scaffold material should not stimulate an adverse immunological response through chemical species present at the implant surface or through possible degradation byproducts (i.e. act as a biocompatible or bioactive material). To date, a number of synthetic polymers have been examined for their ability to serve as tissue engineering scaffolds. These materials have been examined in a number of forms such as particles, foamed porous scaffolds, and fibers, for their ability to initiate bone formation both in vitro an in vivo.
The use of bioactive glass fibers as tissue engineering scaffolds for the regeneration of new bone offers a number of advantages over the other forms mentioned above. The chemistry of this system is such that an immunological response is avoided and instead replaced with a bioactive mechanism. The bioactive glass fibers can undergo a series of chemical reactions leading to the precipitation of a hydroxyapatite (HA) layer on their surface, resulting in a chemical bond to the host tissue (Hench, L L and Wilson, J., “An Introduction to Bioceramics”, World Scientific, 1993). The bioactive glass in turn becomes an integral part of the native tissue. Fabrication of a bioactive glass scaffolds constructed of fibers can provide the necessary structural integrity to maintain mechanical stability while at the same time allowing for the control of porosity, surface area, degradation rate, and the contact guidance of cells. The fibrous system mimics that of the natural collagen fibers orthogonally distributed within native bone providing it with enhanced strength. It is on these collagen fibrils that HA is deposited. In addition, the synthetic nature of the system allows for ease in production, transport and sterilization make it an attractive option as a tissue engineering scaffold.
Bioactive glass fibers have a relatively high silica content that limits their production by the classical high temperature commercial process due to extremely high melt viscosities (Silcar, A., “An Introduction to Glass and Glass Fiber Manufacturing Technology with Application to Nonwoven Process”, Tappi J., 1993; 76:167-174). Na2O and CaO are usually necessary coreactants in conventional processing to adjust the viscosity to levels compatible with fiber pulling. However, the high concentration of Na2O and CaO in bioactive glasses induces crystallization, which ultimately limits the biological activity. Therefore, tradeoffs are generally required.
One way to overcome this problem is through the use of a sol-gel process, as opposed to a melt process, to produce fibers. The sol-gel process uses lower processing temperatures which can reduce crystallization. A sol-gel process involves reactions of hydrolysis and condensation on metal alkoxides that lead to the formation of inorganic chains, rings, and clusters. These reactions can be controlled to produce the required sol structure (colloidal suspension) necessary to fabricate materials such as fibers, films, powders, and gels. Initial conditions of hydrolysis and condensation, such as pH and concentration of agents, can be used to adjust the resulting sol structure.
With regard to fiber pulling, the rheological behavior of the sol is one of the most important processing variables. It is basically accepted that elongated polymers in a solution is the main requirement for spinnability.
Acidic pH values and low molar ratios between water and alkoxide are known to produce linear polymers that exhibit spinnability. On the other hand, high molar ratios between water/alkoxide and a basic medium led to production of spherical and ramified polymers that yield network formation. A low molar ratio of water/alkoxide (2:1) favors generation of a functionality of 2 in the inorganic polymers. The functionality of 2, in this case, refers to the conversion of alkoxide groups to hydroxyl groups, which are more readily condensed and will produce a “linear” polymeric precursor of the sintered fiber. A higher functionality will lead to particle formation, which is undesirable for fiber production. An acidic medium reduces the immiscibility gap in the alcohol-alkoxide-water system and provides a catalytic effect that is also important in the development of linear polymers.
Another important parameter of sol-gel fiber processing that should be optimized is the time between the onset of the spinnability and the gelation time. Disclosed formulations generally exhibit very short gelation times which restrict the production of continuous fibers and the process efficiency.